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Background: Evidence-based mental health interventions to support healthcare workers (HCWs) in crisis settings are scarce. Objective: To evaluate the capacity of a mental health intervention in reducing anxiety and depression symptoms in HCWs, relative to enhanced care as usual (eCAU), amidst the COVID-19 pandemic. Methods: We conducted an analyst-blind, parallel, multicentre, randomised controlled trial. We recruited HCWs with psychological distress from Madrid and Catalonia (Spain). The intervention arm received a stepped-care programme consisting of two WHO-developed interventions adapted for HCWs: Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+). Each intervention lasted 5 weeks and was delivered remotely by non-specialist mental health providers. HCWs reporting psychological distress after DWM completion were invited to continue to PM+. The primary endpoint was self-reported anxiety/ depression symptoms (Patient Health Questionnaire-Anxiety and Depression Scale) at week 21. Findings: Between 3 November 2021 and 31 March 2022, 115 participants were randomised to stepped care and 117 to eCAU (86% women, mean age 37.5). The intervention showed a greater decrease in anxiety/depression symptoms compared with eCAU at the primary endpoint (baseline-adjusted difference 4.4, 95% CI 2.1 to 6.7; standardised effect size 0.8, 95% CI 0.4 to 1.2). No serious adverse events occurred. Conclusions: Brief stepped-care psychological interventions reduce anxiety and depression during a period of stress among HCWs. Clinical implications Our results can inform policies and actions to protect the mental health of HCWs during major health crises and are potentially rapidly replicable in other settings where workers are affected by global emergencies. Trial registration number NCT04980326.

El Trastorno Límite de la Personalidad (TLP) es una entidad diagnóstica que parte de descripciones antiguas, de carácter polimorfo, realizadas por psiquiatras clásicos en las que ya se describían personalidades inestables. Desde los años 80 el diagnóstico de Trastorno Límite aparece en las clasificaciones diagnósticas, siendo este un diagnóstico de cajón de sastre que se ha mantenido hasta la actualidad (DSM-5). El objetivo de esta tesis es estudiar las bases neurobiológicas del trastorno en una cohorte de pacientes estables con TLP, apareados por sexo, coeficiente de inteligencia (CI) y edad con una muestra de controles sanos. La tesis está compuesta por tres trabajos que evalúan: 1) los cambios estructurales mediante resonancia magnética estructural (MRI), 2) los cambios funcionales en resonancia funcional (fMRI) durante la realización de un paradigma cognitivo (la tarea n-back), y 3) los cambios evaluados mediante fMRI en reposo (resting state) y MRI de difusión. Los resultados obtenidos ponen de manifiesto alteraciones estructurales que incluyen reducciones volumétricas de sustancia gris en córtex prefrontal, así como una tendencia al agrandamiento de la amígdala e hipocampo. Por lo que respecta a los hallazgos funcionales con tarea, se detecta un extenso déficit de deactivación que incluye entre otras áreas el nodo anterior de la red neuronal por defecto (Default Mode Network [DMN]). Finalmente, el estudio combinado de resting state y difusión muestra alteraciones convergentes en estructuras genuales y perigenuales junto con anormalidades en la conectividad del circuito fronto-cortico-límbico. Borderline Personality Disorder (BPD) is a diagnostic that was initially used in descriptions from classical psychiatrists, referring to unstable personalities. Since the 80s, BPD appears in main diagnostic classifications as a polymorphous diagnostic that is still found in present classifications (DSM-5). The objective of this thesis is to study the neurobiological bases of the disorder in a sample of stable patients with BPD, matched by sex, IQ and age with a sample of healthy controls. The thesis includes three articles that evaluate: 1) structural changes with structural Magnetic Resonance Imaging (MRI), 2) functional changes with functional MRI (fMRI) acquired while performing a cognitive paradigm (the n-back task), and 3) changes based on resting state fMRI and diffusion MRI images. Results revealed structural alterations including volumetric reductions in gray matter in the prefrontal cortex, as well as a tendency to enlargement of the amygdala and hippocampus. Task related functional findings point to widespread deficits in deactivation involving, among other areas, the anterior node of the Default Mode Network (DMN). Finally, the combined resting state and diffusion MRI study showed converging abnormalities in genual and perigenual structures as well as alterations in the connectivity of the fronto-cortico-limbic circuit.